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Predicting local failure of brain metastases after stereotactic radiosurgery with radiomics on planning MR images and dose maps

Wang, Hesheng; Xue, Jinyu; Qu, Tanxia; Bernstein, Kenneth; Chen, Ting; Barbee, David; Silverman, Joshua S; Kondziolka, Douglas
PURPOSE/OBJECTIVE:Stereotactic radiosurgery (SRS) has become an important modality in the treatment of brain metastases. The purpose of this study is to investigate the potential of radiomic features from planning magnetic resonance (MR) images and dose maps to predict local failure after SRS for brain metastases. MATERIALS/METHODS/METHODS:Twenty-eight patients who received Gamma Knife (GK) radiosurgery for brain metastases were retrospectively reviewed in this IRB-approved study. 179 irradiated tumors included 42 that locally failed within one-year follow-up. Using SRS tumor volumes, radiomic features were calculated on T1-weighted contrast-enhanced MR images acquired for treatment planning and planned dose maps. 125 radiomic features regarding tumor shape, dose distribution, MR intensities and textures were extracted for each tumor. Logistic regression with automatic feature selection was built to predict tumor progression from local control after SRS. Feature selection and model evaluation using receiver operating characteristic (ROC) curves were performed in a nested cross validation (CV) scheme. The associations between selected radiomic features and treatment outcomes were statistically assessed by univariate analysis. RESULTS:The logistic model with feature selection achieved ROC AUC of 0.82 ± 0.09 on 5-fold CV, providing 83% sensitivity and 70% specificity for predicting local failure. A total of 10 radiomic features including 1 shape feature, 6 MR images and 3 dose distribution features were selected. These features were significantly associated with treatment outcomes (p < 0.05). The model was validated on independent holdout data with an AUC of 0.78. CONCLUSIONS:Radiomic features from planning MR images and dose maps provided prognostic information in SRS for brain metastases. A model built on the radiomic features shows promise for early prediction of tumor local failure after treatment, potentially aiding in personalized care for brain metastases.
PMID: 34287940
ISSN: 2473-4209
CID: 5003892

Stereotactic Radiosurgery for Differentiated Thyroid Cancer Brain Metastases: An International, Multicenter Study

Bunevicius, Adomas; Fribance, Sarah; Pikis, Stylianos; Lee, John Y K; Buch, Love Y; Moran, Michael; Yang, Andrew I; Bernstein, Kenneth; Mathieu, David; Perron, Rémi; Liscak, Roman; Simonova, Gabriela; Patel, Samir; Trifiletti, Daniel M; Martínez Álvarez, Roberto; Martínez Moreno, Nuria; Lee, Cheng-Chia; Yang, Huai-Che; Strickland, Ben A; Zada, Gabriel; Chang, Eric L; Kondziolka, Douglas; Sheehan, Jason
PMID: 33978475
ISSN: 1557-9077
CID: 4878392

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA

Kowalchuk, Roman O; Shepard, Matthew J; Sheehan, Kimball; Sheehan, Darrah; Faramand, Andrew; Niranjan, Ajay; Kano, Hideyuki; Gurewitz, Jason; Bernstein, Kenneth; Liscak, Roman; Guseynova, Khumar; Grills, Inga S; Parzen, Jacob S; Cifarelli, Christopher P; Rehman, Azeem A; Atik, Ahmet; Bakhsheshian, Joshua; Zada, Gabriel; Chang, Eric; Giannotta, Steven; Speckter, Herwin; Wu, Hsiu-Mei; Kondziolka, Douglas; Mathieu, David; Lee, Cheng-Chia; Warnick, Ronald E; Lunsford, L Dade; Trifiletti, Daniel M; Sheehan, Jason P
PURPOSE/OBJECTIVE:This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial. METHODS AND MATERIALS/METHODS:From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Statistical methods used included the Kaplan-Meier method, Cox proportional hazards analysis, and recursive partitioning analysis. RESULTS:, and prior radiation therapy or multiple surgeries. The good-prognostic group (score, 0-1) had improved PFS (P < .005) and time to local failure (P < .005) relative to the poor-prognostic group (score, 2-3). Age >50 years (hazard ratio = 1.85 [95% confidence interval, 1.09-3.14]) and multiple prior surgeries (hazard ratio = 1.80 [1.09-2.99]) also portended reduced PFS in patients without prior radiation therapy. Two hundred eighteen of 233 patients in this study qualified for the high-risk group of Radiation Therapy Oncology Group 0539, and they demonstrated similar outcomes (3-year PFS: 53.9% vs 58.8%). The good-prognostic group of SRS patients demonstrated slightly improved outcomes (3-year PFS: 63.1% vs 58.8%). CONCLUSIONS:SRS should be considered in carefully selected patients with atypical meningiomas. We suggest the use of our good-prognostic group to optimize patient selection, and we strongly encourage the initiation of a clinical trial to prospectively validate these outcomes.
PMID: 33548341
ISSN: 1879-355x
CID: 4835422

Commentary: Developing a Professionalism and Harassment Policy for Organized Neurosurgery [Comment]

Kondziolka, Douglas; Markert, James M; McDermott, Michael; Robinson, Shenandoah; Connolly, E Sander
PMID: 33989409
ISSN: 1524-4040
CID: 4889412

Hippocampal sparing in patients receiving radiosurgery for ≥ 25 brain metastases

Kavi, Ami; Gurewitz, Jason; Benjamin, Carolina; Silverman, Joshua; Bernstein, Kenneth; Mureb, Monica; Oh, Cheongeun; Sulman, Erik P; Donahue, Bernadine; Kondziolka, Douglas
PURPOSE/OBJECTIVES/OBJECTIVE:To report our dosimetric analysis of the hippocampi (HC) and the incidence of perihippocampal tumor location in patients with≥25 brain metastases who received stereotactic radiosurgery (SRS) in single or multiple sessions. Materials/Methods Analysis of our prospective registry identified 89 patients treated with SRS for ≥ 25 brain metastases. HC avoidance regions (HA-region) were created on treatment planning MRIs by 5mm expansion of HC. Doses from each session were summed to calculate HC dose. The distribution of metastases relative to the HA-region and the HC was analyzed. RESULTS:Median number of tumors irradiated per patient was 33 (range 25-116) in a median of 3 (range1-12) sessions. Median bilateral HC Dmin (D100), D40, D50, Dmax, and Dmean (Gy) was 1.88, 3.94, 3.62, 16.6, and 3.97 for all patients, and 1.43, 2.99, 2.88, 5.64, and 3.07 for patients with tumors outside the HA-region. Multivariate linear regression showed that the median HC D40, D50, and Dmin were significantly correlated with the tumor number and tumor volume (p <0.001). Of the total3059 treated tumors,83 (2.7%) were located in the HA-region in 57% evaluable patients; 38 tumors (1.2%) abutted or involved the HC itself. CONCLUSIONS:Hippocampal dose, is higher in patients with tumors in the HA-region; however, even for patients with a high burden of intracranial disease and tumors located in the HA-regions, SRS affords hippocampal sparing. This is particularly relevant in light of our finding of eventual perihippocampal metastases in more than half of our patients.
PMID: 34052342
ISSN: 1879-0887
CID: 4890712

Stereotactic Radiosurgery for Atypical (World Health Organization II) and Anaplastic (World Health Organization III) Meningiomas: Results From a Multicenter, International Cohort Study

Shepard, Matthew J; Xu, Zhiyuan; Kearns, Kathryn; Li, Chelsea; Chatrath, Ajay; Sheehan, Kimball; Sheehan, Darrah; Faramand, Andrew; Niranjan, Ajay; Kano, Hideyuki; Gurewitz, Jason; Bernstein, Kenneth; Liscak, Roman; Guseynova, Khumar; Grills, Inga S; Parzen, Jacob S; Cifarelli, Christopher P; Rehman, Azeem A; Atik, Ahmet; Bakhsheshian, Joshua; Zada, Gabriel; Chang, Eric; Giannotta, Steven; Speckter, Herwin; Wu, Hsiu-Mei; Kondziolka, Douglas; Golfinos, John G; Mathieu, David; Lee, Cheng-Chia; Warnick, Ronald E; Lunsford, L Dade; Sheehan, Jason P
BACKGROUND:Atypical and anaplastic meningiomas have reduced progression-free/overall survival (PFS/OS) compared to benign meningiomas. Stereotactic radiosurgery (SRS) for atypical meningiomas (AMs) and anaplastic meningiomas (malignant meningiomas, MMs) has not been adequately described. OBJECTIVE:To define clinical/radiographic outcomes for patients undergoing SRS for AM/MMs. METHODS:An international, multicenter, retrospective cohort study was performed to define clinical/imaging outcomes for patients receiving SRS for AM/MMs. Tumor progression was assessed with response assessment in neuro-oncology (RANO) criteria. Factors associated with PFS/OS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model. RESULTS:A total of 271 patients received SRS for AMs (n = 233, 85.9%) or MMs (n = 38, 14.0%). Single-fraction SRS was most commonly employed (n = 264, 97.4%) with a mean target dose of 14.8 Gy. SRS was used as adjuvant treatment (n = 85, 31.4%), salvage therapy (n = 182, 67.2%), or primary therapy (1.5%). The 5-yr PFS/OS rate was 33.6% and 77.0%, respectively. Increasing age (hazard ratio (HR) = 1.01, P < .05) and a Ki-67 index > 15% (HR = 1.66, P < .03) negatively correlated with PFS. MMs (HR = 3.21, P < .05), increased age (HR = 1.04, P = .04), and reduced KPS (HR = 0.95, P = .04) were associated with shortened OS. Adjuvant versus salvage SRS did not impact PFS/OS. A shortened interval between surgery and SRS improved PFS for AMs (HR = 0.99, P = .02) on subgroup analysis. Radiation necrosis occurred in 34 (12.5%) patients. Five-year rates of repeat surgery/radiation were 33.8% and 60.4%, respectively. CONCLUSION/CONCLUSIONS:AM/MMs remain challenging tumors to treat. Elevated proliferative indices are associated with tumor recurrence, while MMs have worse survival. SRS can control AM/MMs in the short term, but the 5-yr PFS rates are low, underscoring the need for improved treatment options for these patients.
PMID: 33469655
ISSN: 1524-4040
CID: 4861842

Functional connectivity of the default mode, dorsal attention and fronto-parietal executive control networks in glial tumor patients

Tordjman, Mickael; Madelin, Guillaume; Gupta, Pradeep Kumar; Cordova, Christine; Kurz, Sylvia C; Orringer, Daniel; Golfinos, John; Kondziolka, Douglas; Ge, Yulin; Wang, Ruoyu Luie; Lazar, Mariana; Jain, Rajan
PURPOSE/OBJECTIVE:Resting state functional magnetic resonance imaging (rsfMRI) is an emerging tool to explore the functional connectivity of different brain regions. We aimed to assess the disruption of functional connectivity of the Default Mode Network (DMN), Dorsal Attention Network(DAN) and Fronto-Parietal Network (FPN) in patients with glial tumors. METHODS:rsfMRI data acquired on 3T-MR of treatment-naive glioma patients prospectively recruited (2015-2019) and matched controls from the 1000 functional-connectomes-project were analyzed using the CONN functional toolbox. Seed-Based Connectivity Analysis (SBCA) and Independent Component Analysis (ICA, with 10 to 100 components) were performed to study reliably the three networks of interest. RESULTS:). For the FPN, increased connectivity was noted in the precuneus, posterior cingulate gyrus, and frontal cortex. No difference in the connectivity of the networks of interest was demonstrated between low- and high-grade gliomas, as well as when stratified by their IDH1-R132H (isocitrate dehydrogenase) mutation status. CONCLUSION/CONCLUSIONS:Altered functional connectivity is reliably found with SBCA and ICA in the DMN, DAN, and FPN in glioma patients, possibly explained by decreased connectivity between the cerebral hemispheres across the corpus callosum due to disruption of the connections.
PMID: 33528739
ISSN: 1573-7373
CID: 4789692

Stereotactic Radiosurgery for Choroid Plexus Tumors: A Report of the International Radiosurgery Research Foundation

Faramand, Andrew; Kano, Hideyuki; Niranjan, Ajay; Atik, Ahmet F; Lee, Cheng-Chia; Yang, Huai-Che; Mohammed, Nasser; Liscak, Roman; Hanuska, Jaromir; Tripathi, Manjul; Kondziolka, Douglas; Sheehan, Jason; Mathieu, David; Flickinger, John C; Lunsford, L Dade
BACKGROUND:Choroid plexus tumors (CPT) are rare epithelial tumors of the choroid plexus. Gross total resection (GTR) may be curative, but it is not always possible. OBJECTIVE:To evaluate the role of Gamma Knife stereotactic radiosurgery (GKSRS) as either a primary or adjuvant management option for WHO grade I-III CPT through a multicenter project. METHODS:A total of 32 patients (20 females) with a total of 43 treated tumors were included in the analysis. A total of 25 patients (78%) had undergone initial surgical resection. The median total tumor volume was 2.2 cc, and the median margin and maximum doses were 13 and 25.5 Gy, respectively. RESULTS:Local tumor control was achieved in 69% of cases. Local tumor progression-free survival (PFS) rate for low-grade tumors at 1, 3, and 5 yr was 90%, 77%, 58%, respectively. The actuarial local tumor PFS rate for high-grade tumors at 1, 3, and 5 yr was 77%, 62%, and 62%, respectively. There was no significant difference in local tumor control rates between low- and high-grade CPT (P = .3). Gender, age, and degree of resection were not associated with treated tumor PFS. Distant intracranial spread developed in 6 patients at a median of 22 mo after initial SRS. Actuarial distant brain tumor PFS rate at 1, 2, 5, and 10 yr was 93%, 88%, 78%, and 65%, respectively. Three patients (9%) developed persistent symptomatic adverse radiation effects at a median of 11 mo after the procedure. CONCLUSION:GKSRS represents a minimally invasive alternative management strategy for imaging defined or surgically recurrent low- and high-grade CPT.
PMID: 33372216
ISSN: 1524-4040
CID: 4835252

Stem Cell Treatment for Ischemic Stroke Recovery

Kondziolka, Douglas
The role of cellular transplantation to promote functional recovery after stroke has been evaluated over the last two decades. Preclinical studies first established the potential for cultured neuronal cells derived from a teratocarcinoma cell line to be tested for safety and efficacy in the treatment of human stroke. In animal models of stroke that caused reproducible learning and motor deficits, injection of neuronal cells resulted in a return of learning behavior, retention time, and motor function. Clinical trials followed. Additional work with cells derived from a bone marrow neuroprogenitor line, fetal cortical stem cells, and other cell sources showed promise in preclinical studies and then these cells were tested in clinical studies. This report reviews the different biological repair approaches using cell implants, discusses clinical trial design and surgical methods, and the current state of research.
PMID: 33506475
ISSN: 1098-9021
CID: 4800002

Sexual harassment in neurosurgery: #UsToo [Editorial]

Kondziolka, Douglas; Liau, Linda M.
ISSN: 0022-3085
CID: 4990602